Active or passive immunization against proapoptotic neurotrophins for the treatment and/or prevention of neurodegenerative diseases

Abstract

The present invention relates to novel methods for combating cell degeneration or dysfunction resulting from neuroinflammatory conditions. The invention especially relates to the use, in the preparation of a medicament for the treatment of neurodegenerative disease associated with neuroinflammation, of an immunogenic compound which is capable of inducing an immune response against a proapoptotic neurotrophin, or an effective amount of a hapten combined with appropriate carriers and/or adjuvants to render the resulting combination capable of inducing an immune response against a proapoptotic neurotrophin. Also disclosed are compositions for the active or passive immunization against neuronal or glial cell apoptosis caused by neuroinflammation as well as methods and means useful for said active or passive immunization.

1 - 51 . (canceled) 
     
     
         52 . A method of inhibiting neuronal death caused by expression of p75 NTR  in a neuronal or glial cell, in a subject having amyotrophic lateral sclerosis (ALS) or a neurodegenerative disease other than ALS, comprising:
 immunizing the subject with a composition comprising a vehicle and a peptide consisting of SEQ ID NO: 1, or an immunogenic fragment of SEQ ID NO: 1; or   immunizing the subject with a composition comprising a vehicle and a peptide conjugate consisting of SEQ ID NO:1 or an immunogenic or hapten fragment of SEQ ID NO: 1 that has been conjugated to a carrier.   
     
     
         53 . The method of  claim 52 , wherein said subject has amyotrophic lateral sclerosis and the peptide consists of the NGF fragment of SEQ ID NO: 1. 
     
     
         54 . The method of  claim 52 , wherein said peptide is SEQ ID NO: 1. 
     
     
         55 . The method of  claim 52 , wherein said peptide is an immunogenic fragment of SEQ ID NO: 1. 
     
     
         56 . The method of  claim 52 , wherein said composition comprises an adjuvant. 
     
     
         57 . The method of  claim 52 , wherein the subject is immunized with a composition comprising a vehicle and an immunogenic or haptenic fragment of SEQ ID NO: 1 that has been conjugated to a carrier. 
     
     
         58 . The method of  claim 57 , wherein the carrier is selected from the group consisting of bovine serum albumins, immunoglobulin, thyroglobulin, ovalbumin, tetanus toxoid, keyhole limpet hemocyanin, and lipid moieties. 
     
     
         59 . The method of  claim 52 , wherein the subject has a neurodegenerative disease other than ALS. 
     
     
         60 . The method of  claim 59 , wherein the subject has a neurodegenerative disease selected from the group consisting of Alzheimer's disease (AD), Huntington's Disease, Parkinson's Disease, and parkinsonism linked to chromosome 17. 
     
     
         61 . The method of  claim 59 , wherein the subject has frontotemporal dementia. 
     
     
         62 . The method of  claim 59 , wherein the subject has a neurodegenerative disease that is a prion disease. 
     
     
         63 . A method for treating amyotrophic lateral sclerosis (ALS) comprising:
 immunizing the subject with a composition comprising a vehicle and an isolated peptide comprising SEQ ID NO: 1 or a fragment of SEQ ID NO: 1 capable of inducing antibodies to SEQ ID NO: 1 or NGF in said subject, wherein said peptide may be optionally conjugated to an exogenous immunogenic carrier or admixed with an adjuvant, or both.   
     
     
         64 . The method of  claim 63 , wherein said peptide comprises SEQ ID NO: 1. 
     
     
         65 . The method of  claim 63 , wherein said peptide consists of SEQ ID NO: 1. 
     
     
         66 . The method of  claim 63 , wherein said peptide that is an immunogenic fragment of SEQ ID NO: 1. 
     
     
         67 . An agent that inhibits the binding of proapoptotic neurotropin to a neural or glial cell p75 NTR  receptor. 
     
     
         68 . The agent of  claim 67  that comprises a peptide or polypeptide. 
     
     
         69 . The agent of  claim 68 , wherein said peptide or polypeptide is a neurotropin or a fragment of a neurotropin that comprises a binding domain for the p75 NTR  receptor, but which does not bind to p140 trkA . 
     
     
         70 . The agent of  claim 68 , wherein the peptide or polypeptide is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4; or an immunogenic or haptenic fragment comprising at least six consecutive amino acid residues thereof. 
     
     
         71 . The agent of  claim 70 , which is a peptide or polypeptide conjugate that further comprises a carrier that is covalently-coupled to said peptide or polypeptide. 
     
     
         72 . The agent of  claim 71 , wherein said carrier is selected from the group consisting of bovine serum albumin, immunoglobulin, thyroglobulin, ovalbumin, tetanus toxoid, keyhold limpet hemocyanin, and a lipid moiety. 
     
     
         73 . A composition comprising the agent of  claim 67  and a pharmaceutically acceptable vehicle and/or adjuvant. 
     
     
         74 . A method for inhibiting neuronal death or apoptosis caused by the expression of p75 NTR  in a neuronal or glial cell comprising:
 administering to a subject in need thereof an effective amount of the agent of  claim 67 .